Small particles, i.e. particles approaching one micron or less, are known in the art. These particles are made with various techniques and may be comprised of widely varying materials. For example, particles may be made of gold from colloidal gold solutions, tungsten from a process involving grinding, sifting, and filtering, and still other lesser used materials such as stainless steel, frozen water, and plastic spheres. There are still other similarly sized particles made from other materials as well. However, all of these particles produced by these various methods share certain characteristics. For example, the inventor is unaware of any particles, or process for producing particles, which have a uniform size and shape regardless of whether there is an opportunity to choose a particular shape. For example, many processes produce particles which are essentially globular, but those globular shapes vary from particle to particle and also with respect to their size. Still other processes produce particles which have irregular shapes and with particles having different shapes within the same yield. Many of the processes have a significant range in particle size with some of these processes producing particles having less than a smooth distribution in sizes. In other words, there is not a consistent number of particles of each particle size contained within a harvest of any particular process. Furthermore, some particle materials and processes are not capable of being produced in all sizes. Still another limitation in the prior art is that the kinds of materials which may be utilized are process dependent. In other words, certain types of metal may not be used to produce particles through the colloidal solution process due to the chemistry.
For illustrative purposes, the inventor will now describe one particular use of micron-sized particles. These are used in implementing a technology known as biolistics. With this technology, inert or biologically active particles are propelled at cells at a speed whereby the particles penetrate the surface of the cells and become incorporated into the interior of the cells. The process can be used to mark cells or tissue or to biochemically affect tissues or tissue in situ as well as single cells in vitro. There are various kinds of apparatus used to propel the particles into the cells, examples of which are disclosed in U.S. Pat. Nos. 5,371,015; 5,478,744; and 5,179,022, the disclosures of which are incorporated herein by reference. These patents also disclose various uses of the micron-sized particles in the area of biolistics. These uses include gene therapy for the correction of genetic disorders by expressing healthy versions of the defective gene, genetic immunization for eliciting immune responses against specific antigen after inoculating cells with the DNA encoding the antigen, genetic engineering of animals for producing new and useful phenotypes, the determination of functions of genes in an in-vivo setting, and cancer therapy for introducing therapeutic genes into tumorous cells. Again, these uses are only exemplary as biolistics is a relatively new and evolving technology.
As might be expected, it would be desirable in implementing biolistics for a technician to be able to choose both a particle's shape as well as its size and be ensured that a collection of these particles would be uniformly shaped and uniformly sized in order that a uniform effect may be expected upon their use. Furthermore, the particles may be particularly shaped in order to enhance the particular application desired to be implemented. One such example would be to provide particles having an interior surface, much like a donut-shaped particle, so that the interior surface may be filled with a biologically active material desired to be delivered into the cell. Typically, in the prior art as known to the inventor, particles are coated with the biologically active materially and as might be expected some of this biologically active material is lost as the particles are propelled and injected into the cells. This happens through abrasion, acceleration, etc. of the particle's surface as it is delivered.
To the extent that the particle size, shape, and other of its properties can be controlled, new uses for some micron particles may be considered. For example, controlling the particle's size and rendering it magnetizable permits consideration of the particles' use for reliable and safe transportation through a patient's blood system to a desired site with a magnetic field gradient and under computer control. Still other new uses may be considered and are limited solely by the ingenuity of the scientist or engineer.
Also known in the prior art are substrates having arrays of sub-micron sized metal deposits. For example, nanometer size platinum particle arrays were prepared by electron beam lithography. The Pt particles were 50 nm in diameter and spaced 200 nm apart on an oxidized silicon wafer. See P. W. Jacobs, et al., Surface Science, 372, L249-L253 (1997). Another example of e-beam patterning was the preparation of two-dimensional arrays of amorphous R--Co (R=Sm and Gd) square particles on 20 nm thick niobium films. See O. Geoffrey, et al., Journal of Magnetism and Magnetic Materials, 121, 223-226 (1993). A third example involved the deposition of Ni.sub.80 Fe.sub.20 boxes with width and spacing of 1-.mu.m thick on a PMMM resist film, followed by liftoff, which resulted in the production of "box" arrays of 50-nm thick Ni.sub.80 Fe.sub.20 boxes with width and spacing of 1 .mu.m. See A. Maeda, et al., Journal of Applied Physics, 76(10), 6667 (1994). A further example is the production of ultra-small particle arrays by high resolution electron beam lithography, in which arrays of silver and gold-palladium particles smaller than 10 nm in diameter and center-to-center spacings as low as 25 nm were made. See H. Craighead, et al., Journal of Applied Physics, 53(11), 7186 (1982).
Other methods of making metal particle arrays include by "nanosphere lithography" where uniformly sized latex spheres are deposited onto a substrate such that they closest-pack; metal deposition with liftoff results in, for example, triangle shaped particles on a hexagonal lattice. See J. Hulteen, et al., Journal of Vacuum Science and Technology, A 13(3), 1553 (1995). Another approach for making small metal particles is by fabricating them with a scanning tunneling microscope. In one approach, Fe(CO).sub.5 is decomposed by the tunneling electron beam, which results in the deposition on the substrate of small iron deposits with approximate diameter of 25 nm. See A.D. Kent, et al., Journal of Applied Physics, 76(10), 6656 (1994).
Nanoimprint lithography has been used to create metal patterns with feature size of 25 nm and spacing of 70 nm; compression imprinting followed by liftoff of a metal deposited layer results in the 25 nm particles on the substrate. See S. Y. Chou, et al., Science, 272, 85 (1996). These substrates were used with the deposits secured to the substrate and the inventor is unaware of any teaching or suggestion in the prior art that these deposits could be separated from the underlying substrate to produce discrete particles.
To solve these and other problems in the prior art, the inventor herein has succeeded in designing and developing a method of producing micron and submicron particles having a uniform pre-selected shape and size, as well as the particles themselves. With the inventor's process, the composition of each particle, its physical properties and chemical properties, may all be pre-selected or "designed" as desired to satisfy a particular need of the designer. The particles may be made from virtually any material amenable to deposition layering techniques, various different shapes, except perhaps for spheres or globular-shaped particles, of multi-layered construction from dissimilar materials, and engineered to exhibit desirable physical and chemical properties after formation.
Generally, the method of the present invention includes the steps of preparing a substrate and, more particularly, a surface on the substrate for receiving a layer of particle material. This preparation process includes a lithographic patterning of a surface of the substrate with any suitable lithography process. As explained more specifically in the preferred embodiment, the inventor has utilized photolithography including layering the substrate with photoresist and then exposing the substrate through a mask whose pattern is created using a CAD process. However, e-beam lithography, imprint lithography, x-ray lithography, or other kinds of lithographic processes as known in the art may be used as well. After the surface of the substrate is prepared, a layer of material is deposited on the substrate using any appropriate metal deposition process such as vapor deposition, sputter deposition, CVD deposition, or electro-deposition. One or more layers of particle material may be deposited, and the layers may be of the same or dissimilar materials so as to make layered or sandwich type particles. The last step in the process involves separating the particles from the substrate which, depending upon the particular process utilized, may include emerging the substrate in a solvent, vibrating the substrate such as by sonification, or chemical etching, or any other suitable such process. The particles may then be collected and washed thoroughly in order to ready the particles for further use.
The shape, size, and uniformity of the particles is determined and controlled in the lithographic step of preparing the substrate surface. As explained more completely in the detailed description of the preferred embodiment which follows, and in the event that photolithography is utilized, the photo mask pattern helps to determine these parameters. After its preparation, it is used to mask a light exposure for partially burning away a layer of photoresist to create elements for receiving the deposited layers of metal forming the particles. Therefore, it is important to prepare the mask with as accurate an image as is possible to ensure sharp lines and corners (if the particle shape so requires) so that the particles may be shaped and sized as desired.
While several advantages and features of the present invention of a process for making submicron-sized particles and the particles themselves have been explained, a more thorough understanding of the invention may be attained by referring to the drawings attached hereto and by studying the detailed description of the preferred embodiment which is provided for illustrative purposes.